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Role of an anti-inflammatory protein, heme oxygenase-1 in rheumatic and inflammatory diseases

Research Project

Project/Area Number 16590991
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionYokohama City University Graduate School of Medicine

Principal Investigator

TAKENO Mitsuhiro  Yokohama City University, Graduate School of Medicine, Associate Professor, 医学部, 準教授 (50236494)

Co-Investigator(Kenkyū-buntansha) UEDA Atsuhisa  Yokohama City University, Graduate School of Medicine, Associate Professor, 医学部, 準教授 (60295483)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsheme oxygenase-1 / lupus nephritis / Still's disease / hemophagocytic syndrome / ferritin / rhuematoid arthritis / auranofin / heme ooxygenase (HO-1) / 成人発症スティル病 / 金剤 / 腫瘍壊死因子(TNF) / heme oxygenase (HO)-1 / 全身性エリテマトーデス
Research Abstract

The present study investigated roles of heme oxygenase (HO)-1 in rheumatic diseases.
Main results were shown as follows ;
First, weekly administration with an HO-1 inducer, hemin suppresses development of lupus nephritis in MRL/lpr mice by reducing serum anti-DNA antibody level, interferon-γ production, and local expression of iNOS in the kidney. The findings suggest that HO-1 induction therapy is one of promising strategies for lupus nephritis (Takeda Y, Takeno M, et al. Clin Exp Immunol., 2004).
Second, serum HO-1 level is significantly increased in patients with adultonset Still's disease and hemophagocytic syndrome, and that the HO-1 level is closely correlated with disease activity and serum ferritin level, but not cytokines including TNF-α,IL-1,IL-6,IL-8, and IL-18. On the other hand, serum HO-1 level was not elevated in patients having hyperferritinemia due to frequent blood transfusion and liver disorders (Kirino Y, Takeno M et al., Arthritis Research Therapy, 2005). Expression of HO-1 mRNA was not necessarily upregulated in circulating leukocytes from the patients with adult onset Still's disease and hemophagocytic syndrome. Preliminary data indicate that activated macrophages in bone marrow, liver, and lymph nodes may produce HO-1.
Third, HO-1 protein is abundantly expressed in synovial tissues of rheumatoid arthritis. HO-1 expression level in synovial cell lines was inversely correlated with production of proinflammatory cytokines, suggesting the regulatory role of HO-1 in development of inflammation in rheumatoid arthritis. Furthermore, auranofin induces HO-1 expression in synovial cells and the anti-rheumatic pharmacological effects of partly depend on the HO-1 induction (Kobayashi H, Takeno M, et al., Arthritis Rheum, 2006).

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (36 results)

All 2006 2005 2004

All Journal Article (30 results) Book (6 results)

  • [Journal Article] Intestinal manifestations in systemic Iupus erythematosus.2006

    • Author(s)
      Takeno, M., Ishigatsubo, Y.
    • Journal Title

      Intern Med. 45(2)

      Pages: 41-42

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heme oxygenase-1 plays a regulatory role in inflammation in rheumatoid arthritis.2006

    • Author(s)
      Kobayashi H, Takeno M, et al.
    • Journal Title

      Arthritis Rheum 54(4)

      Pages: 1132-1142

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 血球貧食症候群および成人Still病における血清 heme oxygenase-1 (OH-1) の高発現の意義.2006

    • Author(s)
      桐野洋平, 岳野光洋, 他
    • Journal Title

      臨床免疫 45(1)

      Pages: 75-78

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heme oxygenase-1 plays a regulatory role in inflammation in rheumatoid arthritis.2006

    • Author(s)
      Kobayashi H, Takeno M, et al.
    • Journal Title

      Arthritis Rheum 54

      Pages: 1132-1142

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heme oxygenase-1 plays a regulatory role in inflammation in rheumatoid arthritis.2006

    • Author(s)
      Kobayashi H, Takeno M, et al.
    • Journal Title

      Arthritis Rheum (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 血球貪食症候群および成人Stillにおける血清heme oxygenase-1(HO-1)の高発現の意義.2006

    • Author(s)
      桐野洋平, 岳野光洋, 他
    • Journal Title

      臨床免疫 45(1)

      Pages: 75-78

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Excessive expression of Txk, a member of the Tec family of tyrosine kinases, contributes to excessive Th l cytokine production by Tlymphocytes in patients with Behcet's disease.2005

    • Author(s)
      Nagafuchi H, Takeno M, et al.
    • Journal Title

      Clin Exp Immunol. 139(2)

      Pages: 363-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease -use in the differential diagnosis of hyperferritinemia-2005

    • Author(s)
      Kirino Y, Takeno M, et al.
    • Journal Title

      Arthritis Res Ther. 7(3)

      Pages: 616-24

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 炎症性疾患におけるHeme oxygenase-1 (HO-1) の発現.2005

    • Author(s)
      桐野洋平, 岳野光洋, 他
    • Journal Title

      炎症・再生 25(5)

      Pages: 431-435

    • NAID

      10026499123

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Behcet病におけるヘムオキシナーゼ1の役割.2005

    • Author(s)
      岳野光洋, 石ヶ坪良明
    • Journal Title

      医学のあゆみ 215

      Pages: 33-37

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Excessive expression of Txk, a member of the Tec family of tyrosine kinases, contributes to excessive Th1 cytokine production by T lymphocytes in patients with Behcet's disease.2005

    • Author(s)
      Nagafuchi H, Takeno M, et al.
    • Journal Title

      Clin Exp Immunol. 139(2)

      Pages: 363-370

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease : use in the differential diagnosis of hyperferritinemia.2005

    • Author(s)
      Kirino Y, Takeno M, et al.
    • Journal Title

      Arthritis Res Ther. 7(3)

      Pages: 616-624

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Noggin end basic FGF were implicated in forebrain fate end caudal fate respectively, of the neural tube-like structures emerging in mouse ES cell culture.2005

    • Author(s)
      Chiba S, Takeno M, et al.
    • Journal Title

      Exp Brain Res.:,2005 163(1)

      Pages: 86-99

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease : use in the differential diagnosis of hyperferritinemia.2005

    • Author(s)
      Kirino Y, Takeno M et al.
    • Journal Title

      Arthritis Res Ther. 7(3)

      Pages: 616-624

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 炎症性疾患におけるHeme oxygenase-1(HO-1)の発現.2005

    • Author(s)
      桐野洋平, 岳野光洋, 他
    • Journal Title

      炎症・再生 25(5)

      Pages: 431-435

    • NAID

      10026499123

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Behcet病におけるヘムオキシゲナーゼ1の役割.2005

    • Author(s)
      岳野光洋, 石ヶ坪良明
    • Journal Title

      医学のあゆみ 215

      Pages: 33-37

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Noggin and basic FGF were implicated in forebrain fate and caudal fate, respectively, of the neural tube-like structures emerging in mouse ES cell culture.2005

    • Author(s)
      Chiba S, Takeno M, et al.
    • Journal Title

      Exp Brain Res (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Increased serum HO-1 in hemophagocytic syndrome and adult-onset Still's disease -use in the differential diagnosis of hyperferritinemia-2005

    • Author(s)
      Kirino Y, Takeno M, et al.
    • Journal Title

      Arthritis Research and Therapy

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Th l-dominant shift of T cell cytokine production, and subsequent reduction of serum immunoglobulin E response by administration in vivo of plasmid expressing Txk/Rlk, a member of Tec family tyrosine kinases, in a mouse model.2004

    • Author(s)
      Takeno M, et al.
    • Journal Title

      Clin Exp Allergy 34(6)

      Pages: 965-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Abnormal Killer inhibitory receptor expression on natural killer cells in patients with Behcet's disease.2004

    • Author(s)
      Takeno M, et al.
    • Journal Title

      Rheumatol Int 24(4)

      Pages: 212-216

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA antibody2004

    • Author(s)
      Takeda Y, Takeno M, et al.
    • Journal Title

      Clin Exp Immunol. 138(2)

      Pages: 237-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Behcet's disease and inflammatory bowel diseases.2004

    • Author(s)
      Takeno, M., Ishigatsubo, Y.
    • Journal Title

      Intern Med. 43(3)

      Pages: 172-3

    • NAID

      10012708669

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Th1-dominant shift of T cell cytokine production, and subsequent reduction of serum immunoglobulin E response by administration in vivo of plasmid expressing Txk/Rlk, a member of Tec family tyrosine kinases, in a mouse model.2004

    • Author(s)
      Takeno M, et al.
    • Journal Title

      Clin Exp Allergy 34(6)

      Pages: 965-970

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Abnormal killer inhibitory receptor expression on natural killer cells in patients with Behcet's disease.2004

    • Author(s)
      Takeno M, et al.
    • Journal Title

      Rheumatol Int. 24(4)

      Pages: 212-216

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chemical induction of HO-1 suppresses lupus nephritis by reducing local iNOS expression and synthesis of anti-dsDNA antibody.2004

    • Author(s)
      Takeda Y, Takeno M, et al.
    • Journal Title

      Clin Exp Immunol. 138(2)

      Pages: 237-244

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Behcet's disease and inflammatory bowel diseases.2004

    • Author(s)
      Takeno, M., Ishigatsubo, Y.
    • Journal Title

      Internal Med. 43(3)

      Pages: 172-173

    • NAID

      10012708669

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage.2004

    • Author(s)
      Chiba S, Takeno M, et al.
    • Journal Title

      J Neurol Sci 219(1-2)

      Pages: 107-117

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Abnormal killer inhibitory receptor expression on natural killer cells in patients with Behcet's disease.2004

    • Author(s)
      Takeno M, et al.
    • Journal Title

      Rheumatol Int 24(4)

      Pages: 212-216

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of epithelial progenitors in vitro from mouse embryonic stem cells and application for reconstruction of damaged cornea in mice.2004

    • Author(s)
      Homma R, Takeno M, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci. 45(12)

      Pages: 4320-4326

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Behcet's disease and inflammtory bowel diseases.2004

    • Author(s)
      Takeno M, et al.
    • Journal Title

      Internal Med 43(3)

      Pages: 172-173

    • Related Report
      2004 Annual Research Report
  • [Book] year note 2005 (岡庭豊編) 免疫病・アレルギー性疾患・膠原病2005

    • Author(s)
      岳野光洋, 片山一朗
    • Publisher
      メディックメディア、東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] year note 2006別冊 (岡庭豊編) Behcet (ベーチェット病) の診断と治療.2005

    • Author(s)
      岳野光洋
    • Publisher
      メディックメディア、東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] NEWMOOK整形外科(越智隆弘編)2004

    • Author(s)
      阪根剛, 岳野光洋
    • Publisher
      金原出版、東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] year note 2005 (岡庭豊編) 免疫病・アレルギー性疾患・膠原病2004

    • Author(s)
      岳野光洋, 片山一朗
    • Publisher
      メディックメディア、東京
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] リウマチ類縁疾患 NEWMOOK整形外科(越智隆弘編)2004

    • Author(s)
      坂根剛, 岳野光洋, 他
    • Publisher
      金原出版、東京
    • Related Report
      2004 Annual Research Report
  • [Book] year note 2005(岡庭豊編)2004

    • Author(s)
      岳野光洋 他
    • Publisher
      メディックメディア、東京
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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